eplerenone (Rx)

1-10%

Hyperkalemia (2-10%)

Increased risk of hyperkalemia with presence of renal dysfunction

1-3%

• Dizziness
• Fatigue/malaise
• Abdominal pain
• Diarrhea
• Albuminuria
• Hypercholesterolemia
• Hypertriglyceridemia
• Cough

<1%

Abnormal vaginal bleeding

Gynecomastia

Mastodynia

Contraindications

Hypersensitivity

For all patients: Serum potassium >5.5 mEq/L at initiation Creatinine clearance ≤30 mL/min Concomitant use with strong CYP3A inhibitors For the treatment of hypertension: Type 2 diabetes with microalbuminuria Serum creatinine >2.0 mg/dL in males, >1.8 mg/dL in females Creatinine clearance <50 mL/min Concomitant use of potassium supplements or potassium-sparing diuretics

For all patients

• Serum potassium >5.5 mEq/L at initiation
• Creatinine clearance ≤30 mL/min
• Concomitant use with strong CYP3A inhibitors

For the treatment of hypertension

• Type 2 diabetes with microalbuminuria
• Serum creatinine >2.0 mg/dL in males, >1.8 mg/dL in females
• Creatinine clearance <50 mL/min
• Concomitant use of potassium supplements or potassium-sparing diuretics

Cautions

Hyperkalemia, liver dysfunction, metabolic or respiratory acidosis, renal impairment, hypersensitivity to spironolactone

The risk of hyperkalemia is higher in patients with impaired renal function, proteinuria , diabetes and those concomitantly treated with ACEs, ARBs, NSAIDs and moderate CYP3A inhibitors

Patients taking moderate CYP3A inhibitors that cannot be avoided should have their dose of eplerenone reduced

Pregnancy

Available data from published case reports on eplerenone use during pregnancy are insufficient to establish a drug-associated risk of major birth defects, miscarriage, adverse maternal or fetal outcomes; in animal studies, no adverse developmental effects were observed when eplerenone was administered to pregnant rats and rabbits during organogenesis at exposures 32 and 31 times, respectively the human exposure at the 100 mg/day therapeutic dose

Hypertension in pregnancy increases maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage); hypertension increases fetal risk for intrauterine growth restriction and intrauterine death; pregnant women with hypertension should be carefully monitored and managed accordingly

Infertility

• Based on animal data, therapy may compromise male fertility; in mature rates, male fertility was decreased with eplerenone exposure at 17 times the 100 mg/day human therapeutic dose; reversibility of effect, not evaluated

Lactation

There are no human data available on whether eplerenone is present in human milk, or has effects on breastfed infants or on milk production; eplerenone was present in milk of lactating rats; when a drug is present in animal milk, it is likely that the drug will be present in human milk

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Selective aldosterone receptor antagonist; blocks aldosterone binding at the mineralocorticoid receptor

Pharmacokinetics

Half-Life: 3.5-6 hr

Peak Plasma Time: 1-2 hr

Bioavailability: 69%

Protein Bound: 50%

Vd: 43-90 L

Metabolism: primarily hepatic CYP3A4

Metabolite: no active mets identified

Total Body Clearance: 10 L/hr

Excretion: feces (32%) and urine (67%)